Highly efficient three-component synthesis of β-lactams from N-methylhydroxylamine, aldehydes, and phenylacetylene

The three-component reaction of N-substituted hydroxylamines, aldehydes, and phenylacetylene catalyzed by CuCl/2,2'-bipyridine in the presence of NaOAc under neat conditions afforded the corresponding beta-lactams in good to excellent yields. Aromatic, heteroaromatic, and aliphatic aldehydes are tolerated in this reaction. The electronic effects of the aldehydes were studied for the reaction with N-methylhydroxylamine and N-benzylhydroxylamine. For N-methylhydroxylamine, electron-rich aldehydes provided higher yields than electron-deficient aldehydes, whereas for N-benzylhydroxylamine, no significant electronic effect was observed for the aldehydes.